What is the background of the HTA report?

Insured persons and other interested individuals are invited to propose topics for the assessment of medical procedures and technologies through “ThemenCheck Medizin” (Topic Check Medicine) to the Institute for Quality and Efficiency in Health Care (IQWiG). The assessment is done in the form of a health technology assessment (HTA) report. HTA reports include an assessment of medical benefit and health economics as well as an investigation of ethical, social, legal, and organizational aspects of a technology.

In a 2-step selection procedure, which also involves the public, up to 5 new topics are selected each year from among all submitted proposals. According to the legal mandate, these topics should be of particular relevance to patients [1]. IQWiG then commissions external teams of scientists to investigate the topics in accordance with IQWiG methods, and it publishes the HTA reports.

In December 2019, IQWiG commissioned a team of scientists from the University for Continuing Education Krems to investigate the selected topic “HT19-04: Depression in children and adolescents: Does psychotherapy lead to better results when compared with other therapies?”. The team consisted of methodologists experienced in generating HTA reports, experts with knowledge and experience in health economic, ethical, social, legal, and organizational topics as well as a physician specializing in paediatric and adolescent psychiatry and a psychological psychotherapist.

Why is the HTA report important?

Like adults, children and adolescents with depression exhibit typical symptoms such as deep sadness and avolition. However, the disorder may also manifest differently and, e.g. in primary school children, be associated with irritability and outbursts of rage, physical symptoms such as headache or stomachache, or pronounced parental separation anxiety. In adolescents, symptoms including weight fluctuations, drug and alcohol use, extreme sleepiness, and suicidal ideation may suggest depression. Varied symptoms can make it difficult to recognize and diagnose depression at an early stage – particularly since symptoms often overlap with behavioural problems such as aggression and hyperactivity or coincide with other problems such as anxiety or eating disorders.

Up to 1 in 100 children and about 5 in 100 adolescents suffer from depressive disorder [2]. Up to 90% of patients recover from a depressive episode within 1 to 2 years, but more than half of them experience a relapse within 5 years [3,4].

Against this background, a member of the public asked, among other things, whether in children and adolescents, psychotherapy should be started as soon as the first depressive symptoms occur or whether specific therapy should be initially foregone.

Therefore, this HTA report investigates the effects of psychotherapy compared to inactive controls (e.g. waiting list, psychological placebo) with regard to patient-relevant outcomes such as changes in depressive symptoms, suicide risk, or health-related quality of life. Additionally, a comparison with antidepressant therapy or non-drug interventions such as exercise or relaxation exercises was of interest.

Which questions are answered – and which are not?

For this HTA report, medical benefit and harm were assessed on the basis of systematic reviews. In its investigation, the group of authors from the University for Continuing Education Krems included a total of 13 systematic reviews with data from 150 studies of informative value. Studies were found on 3 types of psychotherapy: cognitive behavioural therapy, interpersonal psychotherapy, and psychodynamic psychotherapy. Systemic therapy was excluded a priori since IQWiG has been commissioned by the Federal Joint Committee (G-BA) to assess this therapy [5]. The psychotherapy types were investigated in comparison with inactive controls or with antidepressant therapy and as add-ons to antidepressant therapy. No studies were available for a comparison with non-drug interventions such as exercise and relaxation exercises, which are typically recommended only for mild depression.

The systematic reviews included children and adolescents 4 to 18 years of age. Their analyses typically did not differentiate by age or severity of depression. Therefore, the question about the best approach in children and adolescents with initial mild depressive symptoms cannot be answered on the basis of the included publications. Only general conclusions were drawn:

There were indications of cognitive behavioural therapy and interpersonal psychotherapy alleviating symptoms of depression. An indication was also found for interpersonal psychotherapy effectively helping children and adolescents better manage family, school, and social activities. For psychodynamic psychotherapy, in contrast, there was no hint of alleviation of depressive symptoms. However, limited results are available on psychodynamic psychotherapy because they are based on network metaanalyses which also included studies where fewer than 80% of participants met the inclusion criteria of this HTA report. In addition, the effects of psychotherapies on suicide risk (suicidal ideation and behaviour) were impossible to be reliably assessed even on the basis of these aggregated data since confidence intervals were too wide.

For virtually all investigated outcomes, no hints were found for psychotherapy being more effective than antidepressant therapy nor for antidepressants with add-on psychotherapy being more effective than antidepressant monotherapy. Only for cognitive behavioural therapy administered as an add-on to an antidepressant was there a hint of a long-term advantage in the management of family, school, and social activities.

No systematic review reported any results on all-cause and suicide mortality or health-related quality of life. In addition, no adverse events were investigated, rendering a complete weighing of benefits versus harm impossible.

While the statutory health insurance (SHI) pays for cognitive behavioural therapy and psychodynamic psychotherapy, it does not regularly do so for interpersonal psychotherapy since the SHI catalogue of services currently does not list the latter as an outpatient service. The cost of antidepressants, mental health education, or relaxation therapy are covered for patients with a corresponding diagnosis.

For comparing benefit and cost, 5 health economic studies from the United States and the United Kingdom were found which investigated cognitive behavioural therapy. According to the authors commissioned by IQWiG for this report, however, excessively large differences in healthcare structures made it impossible to adapt these results to the German healthcare context.

On the basis of scoping literature searches and expert interviews, some ethical, social, legal, and organizational aspects related to the disease and the investigated interventions were additionally identified.

The early diagnosis of depression in children and adolescents presents a challenge because its symptoms are often overlapped by other symptoms and comorbidities, or initial symptoms are misinterpreted as typical adolescent or pubescent behaviour. When depression is first suspected, affected people and their family members are often uncertain about how to proceed. Family members do not know whether the situation is hazardous enough to require professional help, and if so, whom to contact. Additionally, concerns about stigmatization can impede early consultation and diagnostic clarification of depressive symptoms. Initial contacts may be general practitioners, paediatricians, and family counselling centres, which refer affected people to psychotherapists, for instance. Additionally, outpatient psychotherapy consultation hours have become available some time ago for seeking advice. If a treatment slot is needed, however, affected people can often expect long waits – particularly if they live in rural areas.

Qualitative research suggests that most patients largely accept psychotherapy and view it as a causative treatment option for depression. According to the commissioned team of scientists, antidepressants, in contrast, tend to be perceived as symptomatic treatment and as associated with potential risks, e.g. dependency or loss of autonomy.

What was discussed in the commenting procedure?

Several comments received by IQWiG regarding the preliminary HTA report noted that current studies on psychodynamic psychotherapy were excluded from the HTA report because the “review of reviews” method was chosen. According to the commentators, a search for primary studies might have resulted in more evidence on the effectiveness of this type of psychotherapy. They added that it was impossible to draw differentiated conclusions by age or severity of depression. In the oral discussion, the group of authors from the University for Continuing Education Krems reiterated that limiting the study analysis largely to systematic reviews is a particularly suitable approach for HTA reports, which are to cover a broad research question on various treatment options and for which many current reviews are available. The authors reviewed the primary studies on psychodynamic psychotherapy which the commentators mentioned as missing from the report. However, these studies did not meet the report’s inclusion criteria. The check of 2 reviews on psychodynamic psychotherapy which were published after completion of the systematic search for the HTA report likewise failed to identify any additional relevant studies.

Furthermore, some commentators suggested answering the member of the public’s initial question more clearly, taking into account the recommendations for action from the S3 guideline “Treatment of depressive disorders in children and adolescents” [6]. In the oral discussion, the authors explained that the objectives of HTA reports differ from those of guidelines. In addition, conclusions were to be drawn only on the basis of the available evidence, rather than adopting recommendations for action from guidelines which are based in part or in full on the opinions of clinical experts.

What’s the next step?

Due to the high disease burden for individuals and their families and the psychological consequences of untreated depression, initial depressive symptoms in children and adolescents should be diagnostically evaluated and, where a diagnosis is established, treated at an early time. Therefore, it seems all the more important for low-threshold services to be available as initial contact points as well as for sufficient therapy slots to exist for patients in this age group.

The HTA report shows that cognitive behavioural therapy and interpersonal psychotherapy can alleviate depressive symptoms in children and adolescents. On the basis of the available literature, however, no conclusion can be drawn as to their effectiveness in patients with various severities of depression or patients of different age groups. The available evidence on psychodynamic psychotherapy is insufficient for drawing a definitive conclusion on effectiveness. When comparing psychotherapy versus antidepressants, there is no evidence of one of the therapies being more effective than the other. However, patients’ individual preferences play an important role in the choice of therapies.

Overall, there is a need for studies of informative value in the German healthcare context. In particular, studies are lacking in psychodynamic psychotherapy as well as in the population of preschool children. Generally, studies should investigate health-related quality of life and adverse events as well as analyse and present results separately by age and severity of depression. Furthermore, longer-term follow-up periods are needed, particularly to more reliably assess the risk of relapse.

References

1.

Sozialgesetzbuch (SGB) Fünftes Buch (V): Gesetzliche Krankenversicherung; (Artikel 1 des Gesetzes v. 20. Dezember 1988, BGBl. I S. 2477) [online]. 2021 [Zugriff: 25.11.2021]. URL: https://www​.gesetze-im-internet​.de/sgb_5/SGB_5.pdf.

2.

Thapar A, Collishaw S, Pine DS, et al. Depression in adolescence. Lancet 2012; 379(9820): 1056-1067. https://dx​.doi.org/10​.1016/S0140-6736(11)60871-4. [PMC free article: PMC3488279] [PubMed: 22305766]

3.

Petermann F. Depressive Störungen im Kindes- und Jugendalter. Gesundheitswesen 2012; 74(8/9): 533-540. https://dx​.doi.org/10​.1055/s-0032-1305259.

4.

Lewinsohn PM, Rohde P, Seeley JR, et al. Natural course of adolescent major depressive disorder in a community sample: predictors of recurrence in young adults. Am J Psychiatry 2000; 157(10): 1584-1591. https://dx​.doi.org/10​.1176/appi.ajp.157.10.1584. [PubMed: 11007711]

5.

Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen. [N21-03] Systemische Therapie bei Kindern und Jugendlichen als Psychotherapieverfahren [online]. 2021 [Zugriff: 25.11.2021]. URL: https://www​.iqwig.de/projekte/n21-03​.html.

6.

Deutsche Gesellschaft für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie. Behandlung von depressiven Störungen bei Kindern und Jugendlichen; Evidenz- und konsensbasierte Leitlinie (S3); AWMF-Registernummer 028 - 043 [online]. 2013 [Zugriff: 25.11.2021]. URL: https://www​.awmf.org​/uploads/tx_szleitlinien​/028-043l_S3_Depressive_St​%C3%B6rungen​_bei_Kindern_Jugendlichen​_2013-07-abgelaufen.pdf.